Native human IL-2 is an antigen-nonspecific, genetically unrestricted soluble factor produced by erythrocyte rosette positive T cells stimulated with antigens, mitogens and alloantigens. It is a protein with a reported molecular weight in the approximate range of 13,000 to 17,000 daltons (S. Gillis and J. Watson, J Exp Med (1980) 159:1709) and an isoelectric point in the approximate range of pH 6-8.5. Human IL-2 has a number of in vitro and in vivo effects including enhancing the proliferative responses of human peripheral blood mononuclear cells or murine thymocytes, enhancing the immune response in humans and in animals against bacterial, parasitic, fungal, protozoan and viral infections, and supporting the growth of continuous T cell lines.
IL-2 and IL-2 muteins in which the cysteine residue at amino acid 125 has been replaced with serine and/or the initial alanine has been eliminated have been produced microbially through genetic engineering techniques. Microbially produced IL-2 is not glycosylated and is produced in a reduced-state by the microorganisms. When purified and oxidized, these microbially produced IL-2s exhibit activity comparable to native human IL-2.
Procedures for purifying native IL-2 from T cells are described by Watson, J., et al, J Exp Med (1979) 150;849-861; Gillis, S., et al, J Immunology (1980) 124:1954-1962; Mochizuki, D. Y., et al, J Immun Meth (1980) 39:185-201; Welte, K., et al, J Exp Med (1982) 156:454-464; and European patent applications No. 83103582.9 (published 26 Oct. 1983 under No. 92163) and No. 83400938.3 (published 16 Nov. 1983 under No. 94317). In general these procedures involve precipitating proteins from culture supernatants with ammonium sulfate followed by a chromatographic fractionation.
Commonly owned copending U.S. patent application Ser. No. 353,360, filed 1 Mar. 1982 and Derynck, R., et al, Nature (1980) 287:193-197 describe procedures for recovering IFN-.beta. from IFN-.beta.-producing E. coli. The patent application describes a procedure in which IFN-.beta. is extracted from cellular material with 2-butanol or 2-methyl-2-butanol.